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Researchers Say Antibody Combined with Tuberculosis Protein Targets Mesothelin

A research team at Massachusetts General Hospital (MGH) says a new drug combination has been effective at extending survival in mouse models of the deadly cancer mesothelioma. According to the team, the two drugs, known as AMD3100 (plerixafor) and VIC-008 (Jantibody), more than doubled the animals’ survival time.

In a recent MGH News Release, Mark Poznansky, Director of the MGH Vaccine and Immunotherapy Center (VIC), said, “We are very excited at the prospect that this drug combination may be much more effective in prolonging patients’ lives.”

The teams’ investigational drug VIC-008, is a fusion protein combining an immune-activating protein from the tuberculosis bacteria with a small antibody fragment targeting mesothelin, a protein expressed in several types of tumors – including mesothelioma, pancreatic, and ovarian cancer. AMD3100 was previously approved for the stimulation of stem cell production prior to bone marrow transplantation.

According to the team, among the mechanisms identified as underlying the combination treatment’s effects was changing a population of immunosuppressive T cells into a type that could enhance an antitumor immune response. “The apparent ability to change immunosuppressive T cells within the tumor into T cell types that are more active and potentially helpful against cancer was a really exciting finding, and one that we’re continuing to investigate,” said Poznansky.

The teams’ series of experiments in two different mesothelioma mouse models found the following:

 

  • While single-agent treatment with either drug had limited effects against mesothelioma, treatment with both drugs significantly reduced tumor size and prolonged the animals’ survival.

 

  • Treatment with VIC-008 increased lymphocyte infiltration of tumors and both the levels and the anti-tumor response of CD8 T cells, which kill damaged or infected cells.

 

  • AMD3100, alone or in combination with VIC-008, decreases expression of the immune checkpoint molecule PD-1 on CD8 T cells, implying that the CXCR4/CXCR12 pathway modulates PD-1 expression.

 

  • AMD3100, alone or in combination, reduced the number of tumor-infiltrating Treg cells and increased the proportion of CD8 T cells.

 

  • AMD3100 further reduces immune suppression by shifting characteristics of Tregs toward those of helper T cells, which would enhance antitumor effects.

 

Jeffrey Gelfand, who collaborated with Poznansky on the study, is an MGH-VIC investigator who developed Jantibody — named in memory of his wife Janet who succumbed to ovarian cancer — as a potential treatment for ovarian cancer. Gelfand notes that, “AMD3100 is already an FDA-approved drug, whose use and application the MGH VIC is hoping to extend in various cancers. We hope these data will help to move Jantibody closer to human tumor therapy, fulfilling one of my wife’s last wishes.”

If you have been diagnosed with mesothelioma, talk to your doctor about investigational treatments such AMD3100 + Jantibody. Innovative treatments such as this could be useful as another line of defense against your specific type of mesothelioma. Talk to your doctor today.

 

Sources

Poznansky, Mark. "Combination Immunotherapy Improves Survival in Mouse Models of Mesothelioma." Massgeneral.org. Massachusetts General Hospital (MGH), 02 Apr. 2018. Web. 16 Apr. 2018.